Multi-tissue adaptive responses of triploid rainbow trout to chronic hypoxia: Effects on antioxidant, inflammatory, mitophagy and apoptosis

Low dissolved oxygen (hypoxia) is among the most pervasive stressors encountered by fish. Triploid rainbow trout ( Oncorhynchus mykiss ), a hypoxia-sensitive species, is particularly vulnerable to hypoxia-induced damage. In this study, we conducted a 31-day chronic hypoxia experiment comparing a normoxic group (dissolved oxygen, DO: 7.73 mg/L) and a hypoxic group (DO: 5.08 mg/L), aiming to explore multi-tissue (gill, brain, liver, heart, and muscle tissue) responses related to antioxidants, inflammation, mitophagy, and apoptosis indicators. The results showed that: 1) Hypoxia significantly increased the expression of Hypoxia-inducible factor-1α (HIF-1α) genes and proteins, whereas HIF-2α exhibited tissue-specific responses. 2) Hypoxia significantly increased the malondialdehyde (MDA) content in the heart, liver, and brain tissues, while antioxidant enzyme activity changed partially across the five tissues. 3) Interleukin-1β ( IL-1β ), Tumor Necrosis Factor-alpha ( TNF-α ), and Interleukin-10 ( IL-10 ) were significantly up-regulated in gills, brain, heart, and muscle tissues ( p < 0.05), while Interleukin-4 ( IL-4 ) was significantly improved ( p < 0.01), and IL-10 was significantly decreased in the liver ( p < 0.05). 4) Hypoxia markedly enhanced the expression of apoptosis-related genes and proteins. 5) Hypoxia activated the expression of mitophagy-related genes and proteins, but key regulators PINK1 and Parkin were significantly down-regulated in the gills. In summary, chronic hypoxia induces significant multifaceted tissue-specific perturbations, which triploid rainbow trout mitigate through coordinated regulation of multiple cellular pathways centered on the Hypoxia-inducible factor (HIF) family, exhibiting distinct adaptive characteristics in each tissue to cope with long-term hypoxia. • Chronic hypoxia upregulated HIF-1α in all tissues, while HIF-2α rapidly accumulated in the gill. • Five tissues adopted distinct strategies: gill mitophagy, brain antioxidation, liver dual mitophagy, heart apoptosis, muscle Nrf2. • Oxidative stress, inflammation, mitophagy, and apoptosis formed a tissue-specific sensing-defense-repair network. • Muscle showed decreased MDA and Nrf2-driven antioxidant gene activation, indicating strong resilience. • This study clarifies teleost hypoxia adaptation, informing conservation and aquaculture under climate change.