Balancing dietary n−3 long-chain polyunsaturated fatty acids (LC-PUFAs) is essential for optimizing growth and disease resilience in Atlantic salmon and will become an increasing challenge when implementing novel sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), such as genetically modified (GM) oils and microalgae oils. To study this, Atlantic salmon (Salmo salar L.) fry (initial weight 0.15 g) were pre-fed diets differing in EPA/DHA ratios (0.2 E/D, 0.9 E/D, and 2.2 E/D) while maintaining constant total EPA+DHA for 4 weeks. Following this, and while kept on the same dietary treatments, the fry were challenged with wild-type or attenuated salmonid alphavirus (SAV-WT and SAV-Att, respectively). The duration of the disease challenge was up to 28 days, with a final fish weight of approximately 1.1 g at the end of the trial. There was a clear decrease in fatty acid storage during SAV-WT infection, which was not observed during SAV-Att infection. We demonstrate a preferential decrease in monounsaturated fatty acids during SAV-WT infection, preserving the n−3 LC-PUFA content in the tissues. Increasing the dietary EPA/DHA ratio significantly reduced growth performance, indicating that the dietary balance of EPA to DHA influences growth during the start feeding of salmon fry. Following infection, dietary effects were outcome-dependent. Fish fed the low EPA/DHA diet (0.2 E/D) showed overall higher viral loads, but improved histopathology at the end of the trial. In contrast, fish fed the high EPA/DHA diet (2.2 E/D) exhibited signs of improved histopathology at the end of the trial, yet experienced the highest (non-significant) mortality after SAV-WT challenge. Fish fed the balanced diet (0.9 E/D) showed poorer histopathological scores at the end of the trial, but did not display elevated mortality. These findings demonstrate that dietary EPA/DHA ratios differentially modulate growth and disease outcome, exerting distinct and sometimes opposing effects on viral load, tissue inflammation, and survival. The results highlight the complexity of optimizing n−3 LC-PUFA balance to support both performance and antiviral resilience in Atlantic salmon.
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