RNA-Seq reveals molecular strategies in response to chronic hypoxic challenge in the gills of Takifugu rubripes

Abstract Hypoxia negatively affects fish behavior, growth, physiological metabolism, and immune responses, or even death. Due to the high density of breeding, sudden power outages and hypoxia stresses have become a serious problem for the aquaculture of Takifugu rubripes. As fish gills are the first organ to be affected by hypoxia in the aquatic environment, the ability to sense and respond to hypoxic stress is crucial. At the molecular level, therefore, the regulation of gene expression in the gills is essential for hypoxia tolerance. Using an RNA-Seq approach in the Illumina sequencing platform, we investigated transcriptome modulation in the gills of T. rubripes, in response to chronic hypoxic stress (2.5 ± 0.5 mg/L for 10 days). Transcriptomic analysis showed that 143 differentially expressed genes (DEGs) (|log2foldchange| >=1 & p.adj < 0.05) were detected under chronic hypoxic exposure (84 up-regulated and 59 down-regulated genes). According to GO annotation, KEGG, and GSEA enrichment analysis, we found that chronic hypoxia can cause damage to animal tissues. However, the functional analysis also showed that T. rubripes can improve the ability to resist hypoxic stress by changing the expression of genes related to metabolic processes and O2 extraction. Of particular interest was the activated immune-related pathways, including Cytokine-cytokine receptor interaction and CCR chemokine receptor binding, which play an essential role in the adaptation of T. rubripes to chronic hypoxic stress. Therefore, the regulated genes and pathways identified in this study enrich the molecular regulatory mechanism of T. rubripes in different hypoxic conditions, which is valuable for further studies regarding hypoxia tolerance in T. rubripes and other teleost fish, and pave the way for future research to understand the tissue-specific molecular responses to hypoxic stress.