We isolated and identified Aeromonas salmonicida subsp. masoucida RFAS1 from diseased black rockfish (Sebastes schlegeli Hilgendorf) showing ulcer lesions on their body during winter of 2008 and spring of 2009. In this study, we tried to understand physiological responses occurring in black rockfish infected with RFAS1 through co-expression and DEG analysis from head kidney RNA-seq data. Black rockfish (average B.W.=19g, n=100/group) were intraperitoneally injected with low (7.7 x 105 CFU/fish; L-group) and high (3.4 x 107 CFU/fish; H-group) concentration of RFAS1. From iso-seq (PacBio) data, 78,142 unigenes were produced and used as reference and thus about 90% of reads generated from Illumina Hiseq 2500 were mapped on those unigenes. Mortality in each group were 5% and 30% over 7 days, respectively. For transcriptome analysis, head kidney samples (n=3/group) were selected from each group at dpc 1 and 5 based on proportion of leukocytes through flow cytometry; control-dpc0 (0D), low-dpc1 (L-1D), low-dpc5 (L-5D), high-dpc1 (H-1D) and high-dpc5 (H-5D). Co-expression analysis was performed using the WGCNA (weighted gene co-expression network analysis) package with 34,370 unigenes (FPKM > 0.1). Significant modules (|GSvsMM| >0.5, p-value <0.05) were selected and analyzed using KEGG and GO. Protein processing in endoplasmic reticulum and adipocytokine signaling pathway were up-regulated in H-groups. Genes involved in TNF signaling pathway, C-type lectin receptor signaling pathway, and apoptosis were up-regulated only in H-5D. However, genes in platelet activation, lysine degradation, focal adhesion were down-regulated in H-groups, and cell cycle and human T-cell leukemia virus 1 infection were up-regulated in L-1D and H-5D. genes in peroxidase activity and MHC class I protein complexes were up-regulated at late stage in L-group. And, apoptosis, necroptosis, complement cascades activities were up-regulated, but peroxidase activity and MHC class II protein complex and binding activities were down-regulated at late stage in H-group. And in addition to all these pathways, NOD-like receptor signaling pathways were changed significantly higher compared to L-group. This transcriptome approach facilitates new insights into understanding of global fish-pathogen interactions including immune responses.