Comparative Gill Transcriptomics Reveals Unresolved Inflammation Under Chronic Hypoxia and Molecular Plasticity During Cyclic Hypoxia in Salmo salar

Global aquaculture faces increasing threats from declining oxygen levels, with several key aquaculture regions now classified as hypoxic. The gills, responsible for oxygen uptake, pathogen-sensing, and immune responses, are the primary interface for this stress. However, the comparative effects of different hypoxic regimes on the gill resilience of Atlantic salmon (Salmo salar) remain poorly understood. In this study, Atlantic salmon were exposed during a 7-day trial to two different moderate hypoxic stress models, chronic hypoxia and cyclic hypoxia. A whole-genome oligo-microarray revealed that both hypoxic stress regimes cause transcriptomic shifts, driven in the chronic hypoxia group by upregulation of PRRs and other immune components and downregulation of DNA repair and cell cycle maintenance. On the other hand, the cyclic hypoxic group focused on physiological plasticity and rapid cellular adjustments. Additionally, RT-qPCR was used to evaluate key gene expression of hypoxia and immune response. The chronic hypoxia group was characterized by downregulation of hif2a, gshpx, and gr-anx1 signaling, with a continuous upregulation state of tnfa2, suggesting an unresolved inflammatory state, often associated with apoptosis and gill damage. In contrast, the cyclic hypoxia group displayed an increased epo expression and recovery of antioxidant enzymes (e.g., gsphx), accompanied by normalized levels of tnfa2 at the end of the 7-day trial. Therefore, chronic hypoxic stress imposes a significantly higher burden on the gills of Atlantic salmon than cyclic hypoxic stress, compromising their ability to respond to secondary stressors and impairing immune homeostasis.