Transcriptome sequencing provides insights into the mechanism of hypoxia adaption in bighead carp (Hypophthalmichthys nobilis)

Hypoxia negatively affects the behavior, immunology, physiology, and growth of fish. Therefore, uncovering the genetic mechanisms underlying hypoxia adaptation and tolerance in fish prior to any genetic improvement is essential. Bighead carp is one of the most important freshwater fish species in aquaculture worldwide; however, this species does not have a strong ability to tolerate hypoxia. In this study, the dissolved oxygen level (0.6 mg/L) was maintained above the asphyxiation point of bighead carp for a long time to simulate hypoxia stress. The liver, gills, and heart were sampled before (0 h) and after (1 h, 2 h, 4 h) the hypoxia tests. Glutathione peroxidase (GPx) and catalase (CAT) activities and malondialdehyde (MDA) levels in the liver were significantly (p < 0.05) elevated at 1 h after hypoxic stress. By observing tissue morphology, the cell structure of the liver and gill tissues was found to change to varying degrees before and after hypoxia stress. Transcriptome sequencing was performed on 36 samples of gill, liver, and heart at four time points, and a total of 293.55G of data was obtained. In the early phase (0-1 h), differentially expressed genes (DEGs, 807 genes upregulated, 654 genes downregulated) were mainly enriched in signal transduction, such as cytokine-cytokine receptor interactions and ECM-receptor interactions. In the middle phase (0-2 h), DEGs (1201 genes upregulated and 2036 genes downregulated) were mainly enriched in regulation and adaptation, such as the MAPK and FoxO signaling pathways. Finally, in the later phase (0-4 h), DEGs (3975 genes upregulated and 4412 genes downregulated) were mainly enriched in tolerance and apoptosis, such as the VEGF signaling pathway and apoptosis. The genes with the most remarkable upregulation at different time points in the three tissues had some similarities. Genetic differences in these genes may be responsible for the differences in hypoxia tolerance among individuals. Altogether, our study provides new insights into the molecular mechanisms of hypoxia adaptation in fish. Further, the key regulatory genes identified provide genetic resources for breeding hypoxia-tolerant bighead carp species.