Balancing Omega-3 Fatty Acids Shapes Growth and Viral Disease Outcomes in Young Salmon

Atlantic salmon farming has long depended on fish oil and fishmeal to supply two essential long-chain omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These molecules have traditionally arrived in feed in roughly equal proportions, but as the aquaculture industry searches for sustainable alternatives to finite marine resources, that balance is changing. Genetically modified oilseed crops and microalgae oils promise new supplies of EPA and DHA, yet many of these novel ingredients carry skewed ratios of the two fatty acids. A new study published in Frontiers in Aquaculture shows that this ratio matters far more than previously appreciated, influencing not only how fast young salmon grow but also how they fare when infected with a serious viral pathogen.

Researchers at the Institute of Marine Research in Bergen, Norway, working with colleagues at the Norwegian Veterinary Institute, designed a carefully controlled feeding trial with Atlantic salmon fry at the very start of exogenous feeding. The fish, weighing just 0.15 grams at the outset, were fed one of three diets for four weeks. All three diets contained the same total amount of EPA plus DHA, approximately 29 percent of total fatty acids, but differed in the ratio between them: one was DHA-dominant with an EPA/DHA ratio of 0.2, one was balanced at 0.9, and one was EPA-rich at 2.2. The diets were formulated to be identical in protein, lipid, saturated fatty acids, monounsaturated fatty acids, and total polyunsaturated fatty acids, isolating the effect of the ratio itself. After the pre-feeding period, the fry were challenged by injection with either wild-type salmonid alphavirus subtype 3 (SAV3), the causative agent of pancreas disease, or an attenuated laboratory strain engineered through codon pair bias de-optimization, which introduces hundreds of synonymous genetic changes that reduce virulence while preserving tissue tropism.

The first major finding concerned growth. After four weeks of pre-feeding, fry fed the EPA-rich diet (2.2 E/D) weighed significantly less than those fed the DHA-rich diet (0.2 E/D), with the balanced group intermediate. This result challenges the prevailing assumption that the EPA/DHA ratio is largely irrelevant to salmon growth, an assumption partly rooted in earlier trials that varied total EPA plus DHA alongside the ratio, confounding the two effects. Because the Norwegian team held total omega-3 content constant, the growth penalty could be attributed more confidently to the ratio itself, or to an inadequate supply of DHA in the high-EPA diet, whose DHA content fell to just 9 percent of total fatty acids compared with 24 percent in the DHA-rich diet.

The authors propose several mechanisms to explain the growth reduction. When dietary DHA is scarce relative to EPA, salmon appear to activate elongation and desaturation pathways to biosynthesize DHA from EPA, a metabolically costly process. Consistent with this, fry on the high-EPA diet maintained whole-body DHA levels roughly 1.6 times higher than their feed contained, and levels of docosapentaenoic acid, an intermediary in the biosynthetic pathway, rose with dietary EPA despite declining dietary DPA. Alternatively, EPA is more readily beta-oxidized for energy than DHA, which is preferentially retained in membranes, so an EPA-heavy diet may divert fatty acids away from storage. Reduced feed intake or intestinal inflammation under low-DHA conditions remain additional possibilities, though feed intake could not be measured precisely in this experimental system.

When it came to infection, the two viral strains behaved as expected but revealed different facets of the dietary effect. Wild-type SAV3 proved highly virulent: viral loads were uniformly high across all fish by seven days post-challenge, histopathological lesions appeared in the heart, pancreas, and muscle, and mortality began around day 17, forcing the researchers to terminate the wild-type arm early at day 19. Cumulative mortality reached 28.3 percent in the DHA-rich group, 23.2 percent in the balanced group, and 45.5 percent in the EPA-rich group, a nearly twofold difference that did not reach statistical significance but suggests the high-EPA diet may have worsened survival. The attenuated virus, by contrast, caused no mortality and milder tissue damage, and its lower, more variable viral loads allowed individual host factors to shape infection kinetics in the early phase.

One of the most striking observations came from whole-body fatty acid analysis. Wild-type SAV3 infection triggered a dramatic depletion of stored lipids, with absolute concentrations of nearly every fatty acid falling. The losses were selective: monounsaturated fatty acids such as oleic acid, the most expendable pool, declined the most, while long-chain polyunsaturated fatty acids like DHA and arachidonic acid were relatively preserved and their proportional share of the remaining lipid pool actually increased. This pattern suggests the infected fry prioritized retaining the fatty acids needed for membrane integrity and inflammatory lipid mediator production, sparing them from oxidation. Notably, this lipid mobilization was almost entirely absent in fry infected with the attenuated virus, whose tissue fatty acid profiles remained close to dietary expectations, consistent with the milder pancreatic damage and reduced metabolic disruption caused by that strain.

Viral load measurements revealed a significant three-way interaction between diet, virus type, and time. Among fry infected with the attenuated virus, those fed the DHA-rich diet carried significantly higher viral loads at seven days post-challenge than the other dietary groups. Yet this early viral advantage did not translate into worse outcomes; the DHA-rich fish ultimately showed improved histopathology at the end of the trial. The authors speculate that insufficient EPA may have weakened early innate antiviral signaling, permitting higher initial replication, while abundant DHA, a precursor for specialized pro-resolving mediators that actively resolve inflammation, promoted better tissue recovery later in the disease course.

The EPA-rich diet told a different story. Fish on this diet showed signs of improved histopathology at the final sampling, echoing earlier reports that high-EPA functional feeds reduce heart inflammation and lesions in salmon viral diseases, but they also suffered the highest, if statistically non-significant, mortality after wild-type challenge. The balanced diet produced yet another combination: poorer histopathological scores at the end of the trial but no elevated mortality, and only minor infection-driven changes in tissue fatty acid composition. These divergent patterns, the researchers emphasize, demonstrate that viral load, tissue inflammation, and survival can be modulated independently and sometimes in opposing directions by the same dietary manipulation, making it impossible to declare a single optimal ratio for disease resilience.

Beyond its nutritional findings, the study validates the salmon fry as a sensitive experimental model for nutrition-disease interactions and highlights the complementary value of the two viral strains. Wild-type SAV3 reflects the severe infections encountered in commercial aquaculture, where pancreas disease ranks among the leading causes of seawater mortality in Norway, but its rapid progression and lethality limit its usefulness for detecting subtle dietary effects. The attenuated strain, engineered through codon pair bias de-optimization that introduced 882 synonymous nucleotide changes while preserving genomic characteristics such as codon usage and RNA folding energy, offers a non-lethal model in which longer-term effects of feed composition on immune responses and inflammation resolution can be observed. The authors caution that viral loads in all wild-type-challenged groups declined before mortality peaked, reinforcing earlier evidence that viral load magnitude does not correlate directly with disease severity, and that histopathology may track mortality more closely.

The practical implications are considerable. As fish oil inclusion in salmon feeds continues to fall and novel EPA and DHA sources with imbalanced compositions enter the market, feed formulators will need to consider the ratio between these fatty acids, not merely their sum. The finding that an EPA-rich diet impaired growth in fry, consistent with results previously reported in post-smolts, suggests that DHA supply may be inadequate even at levels once considered sufficient, and that the metabolic cost of compensatory DHA biosynthesis carries a measurable price. At the same time, the disease data show that neither a DHA-dominant nor an EPA-dominant diet is uniformly protective, and that the optimal balance may depend on which outcome matters most at a given stage of infection. The authors call for longer follow-up studies capturing the recovery phase, and for analyses of EPA- and DHA-derived lipid mediators, which could reveal immunological effects of altered fatty acid profiles that bulk composition measurements cannot detect. For an industry betting its omega-3 future on algae and genetically modified oils, the message is clear: how much EPA and DHA a feed contains is only half the story, and how they are balanced may determine whether farmed salmon grow well, resist viral disease, or both.

Subject of Research: Effects of dietary EPA/DHA ratios on growth and salmonid alphavirus disease response in Atlantic salmon fry

Article Title: Varying dietary EPA/DHA ratios influence growth and viral disease response in Atlantic salmon (Salmo salar L.) fry

Article References: Zhuang, Z., Hundal, B. K., Belghit, I., Adam, A.-C., Sindre, H., Grove, S., & Liland, N. S. (2026). Varying dietary EPA/DHA ratios influence growth and viral disease response in Atlantic salmon (Salmo salar L.) fry. Frontiers in Aquaculture, 5, Article 1860524. https://doi.org/10.3389/faquc.2026.1860524

Image Credits: AI Generated

DOI: 10.3389/faquc.2026.1860524

Keywords: Atlantic salmon, EPA, DHA, omega-3 fatty acids, salmonid alphavirus, pancreas disease, aquaculture nutrition, fish health, viral infection, fatty acid metabolism, antiviral resilience, salmon fry