| Summary: | The large yellow croaker (<i>Larimichthys crocea</i>) is an important marine economic fish in China; however, its intolerance to hypoxia causes widespread mortality. To understand the molecular mechanisms underlying hypoxia tolerance in <i>L. crocea</i>, the transcriptome gene expression profiling of three different tissues (blood, gills, and liver) of <i>L. crocea</i> exposed to hypoxia and reoxygenation stress were performed. In parallel, the gene relationships were investigated based on weighted gene co-expression network analysis (WGCNA). Accordingly, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that several pathways (e.g., energy metabolism, signal transduction, oxygen transport, and osmotic regulation) may be involved in the response of <i>L. crocea</i> to hypoxia and reoxygenation stress. In addition, also, four key modules (darkorange, magenta, saddlebrown, and darkolivegreen) that were highly relevant to the samples were identified by WGCNA. Furthermore, some hub genes within the association module, including <i>RPS16, EDRF1, KCNK5, SNAT2, PFKL, GSK-3β,</i> and <i>PIK3CD,</i> were found. This is the first study to report the co-expression patterns of a gene network after hypoxia stress in marine fish. The results provide new clues for further research on the molecular mechanisms underlying hypoxia tolerance in <i>L. crocea</i>.
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