The late blight pathogen Phytophthora infestans can attack both potato foliage and tubers. When inoculated with P. infestans, foliage of nontransformed 'Russet Burbank' (WT) develops late blight disease while that of transgenic 'Russet Burbank' line SP2211 (+RB) does not. We compared the foliar transcriptome responses of these two lines to P. infestans inoculation using an RNA-seq approach. A total of 515 million paired end RNA-seq reads were generated, representing the transcription of 29,970 genes. We also compared the differences and similarities of defense mechanisms against P. infestans in potato foliage and tubers. Differentially expressed genes, gene groups and ontology bins were identified to show similarities and differences in foliage and tuber defense mechanisms. Our results suggest that R gene dosage and shared biochemical pathways (such as ethylene and stress bins) contribute to RB-mediated incompatible potato-P. infestans interactions in both the foliage and tubers. Certain ontology bins such as cell wall and lipid metabolisms are potentially organ-specific.