Channel catfish and blue catfish represent two economically important freshwater aquaculture species in the United States. Our study aims to investigate the gene expression differences between these two catfish species by high-throughput RNA sequencing to understand their associated phenotypic differences in growth and disease resistant. Our transcriptomic analyses provide some insights into gene function differences between the two species and the molecular basis of channel catfish growth advantage in the tank culture environment. Overall design: Muscle, liver, intestine, mucus, and heart of channel catfish and blue catfish with three replicates were collected for RNA sequencing to identify the differentially expressed genes and tissue-specifically expressed genes.