Parasites are strong drivers of evolutionary change and the genetic variation of both host and parasite populations can co-evolve as a function of parasite virulence and host resistance. The role of transcriptome variation in specific interactions between host and parasite genotypes has been less studied and can be confounded by differences in genetic variation. We employed two naturally inbred lines of a self-fertilizing fish to estimate the role of host genotype in the transcriptome response to parasite infection using RNA-seq. In addition, we targeted several differentially expressed immune-related genes to further investigate the relative role of individual variation in the immune response using RT-qPCR, taking advantage of the genomic uniformity of the self-fertilizing lines. We found significant differences in gene expression between lines in response to infection both in the transcriptome and in individual gene RT-qPCR analyses. Individual RT-qPCR analyses of gene expression identified significant variance differences between lines for six genes but only for three genes between infected and control fish. Our results indicate that although the genetic background plays an important role in the transcriptome response to parasites, it cannot fully explain individual differences within genetically homogeneous lines, which can be important for determining the response to parasites.