Transcriptome Analysis Reveals the Effects of Dietary DHA and EPA on the Hepatic Response to Unpredictable Chronic Stress in Atlantic Salmon (Salmo salar L.)

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are key long-chain omega-3 fatty acids in fish nutrition, but their differential effects on Atlantic salmon under unpredictable chronic stress (UCS) remain unclear. This study compared hepatic responses to DHA- and EPA-rich diets under unstressed and UCS conditions. Atlantic salmon post-smolts were fed a low-EPA+DHA, DHA-rich, or EPA-rich diet for 10 weeks, followed by 3 weeks of UCS. Liver transcriptomes were analyzed by RNA sequencing, and selected genes were validated by quantitative reverse transcription PCR. Growth did not differ among dietary groups. Under unstressed conditions, the DHA-rich diet induced more differentially expressed genes than the EPA-rich diet (67 vs. 29) and affected pathways related to fatty acid metabolism, autophagy, cholesterol homeostasis, and antioxidant defense. After UCS, the EPA-rich diet induced a broader hepatic transcriptional response than the DHA-rich diet (205 vs. 57 differentially expressed genes), with only 12 genes shared between the two comparisons. Both diets affected fatty acid- and steroid-biosynthesis-related pathways, while gene-level responses were diet-specific. These findings reveal distinct, stress-dependent hepatic responses to dietary DHA and EPA and may inform future optimization of their nutritional provision in Atlantic salmon production.