The plant innate immune response is mediated by resistance (R) genes and involves hypersensitive response (HR) cell death. During resistance responses, the host undergoes net changes in the transcriptome. To understand these changes, we generated a whole genome transcript profile for RCY1-mediated resistance to cucumber mosaic virus strain Y (CMV-Y) in Arabidopsis. Using a very stringent selection criterion, we identified 444 putative factors belonging to nine different functional classes that show significant transcript regulation during Arabidopsis-CMV-Y interaction. Genes with unknown function formed the largest class. Other functional classes represented in the resistome include kinases and phosphatases, protein degradation machinery/proteases, transcriptional regulators, and others. Interestingly, several of the unknown function genes possess well characterized domains and secondly many genes encode small peptides with less than 100 amino acids. Analysis of 1.1 kb promoter regions of the 444 genes revealed that 9 out of the 12 known cis-binding elements are significantly associated with pathogen responsive cluster. Location and distribution of five prominent binding elements for select group of disease resistance related and unknown function genes is presented. The analysis also revealed 80 defense-responsive genes that might participate in R gene-mediated defense against both viral and bacterial pathogens. In addition, chromosome distribution of genes that respond to bacterial and viral pathogens suggests that they are located in small gene clusters and may be transcriptionally co-regulated. Exploring the precise function of the new genes identified in this analysis will offer new insights into plant defense.