In our study, transcriptional profiles of the Mytilus coruscus closed shell muscles, gills, and mantle were examined 24 h after V. alginolyticus injection. We then performed bioinformatics analysis, including screening of differentially expressed genes (DEG), Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The results of this study will lay a theoretical foundation for future studies on the immune mechanism of Vibrio alginolyticus infection in bivalves and provide an important and valuable resource for the Mytilus coruscus culture.