Infectious disease outbreaks in aquaculture form major setbacks to fish production and to further development of this important sector. Cyprinid herpes virus-3 (CyHV-3) is a dsDNA virus widely affecting production of common carp (Cyprinus carpio), one of the most farmed fish species worldwide. Genetically disease resistant strains are highly sought for a sustainable solution to this problem. To study the genetic basis and cellular pathways underlining CyHV-3 resistance in common carp, RNA-Seq was used to characterize transcriptional responses of susceptible and resistant fish at day 4 after CyHV-3 infection. Understanding resistance mechanisms is important both for development of both vaccines and resistant strains and lays the foundation for future studies in this field.