The eastern slope of the Grand Banks, Newfoundland and Labrador, Canada, represents an area where active seismic exploration overlaps extensively with an important snow crab (Chionoecetes opilio) fishery. This project investigated the potential impact of 2D seismic noise exposure on the snow crab hepatopancreas transcriptome with a focus on immune, digestion, metabolism and stress-response relevant gene expression. Briefly, snow crab were captured from a control site (Lilly Canyon: 44 54.00 N, 49 13.50 W) and an experimental site (Carson Canyon: 45 27.00 N, 48 43.00 W) located 70 km away. At Carson Canyon, snow crab were subjected to seismic noise for 2 h from an industry seismic survey vessel using an airgun array with a total volume of 4880 cubic inches, with shots at 10 s intervals, operated at 2000 psi and deployed at 9 m of depth. The horizontal zero-to-peak sound pressure level was 251 dB re 1 µPa @ 1 m and the source sound exposure level was 229 dB re 1 µPa2·s @ 1m. Snow crab were captured before, and 18 h and 3 weeks after seismic exposure. RNA was isolated from the hepatopancreas of 10 crab from each of the four groups and subjected to RNA sequencing (RNAseq) analyses. A comparison of the transcriptome of individuals from the four groups was performed using both DESeq2 and edgeR (FDR < 0.05). Real-time quantitative polymerase chain reaction (qPCR) assays were designed for a subset of differentially expressed transcripts to validate the RNAseq results these genes are candidate seismic-responsive molecular biomarkers.