Black shank, caused by Phytophthora nicotianae (P. nicotianae), is a serious disease of cultivated tobacco (Nicotiana tabacum) worldwide. The interactions between tobacco and P. nicotianae are complex and the outcomes of the interactions depend on the tobacco genotype, P. nicotianae strain, and environmental conditions. In this study, we used RNA-sequencing (RNA-Seq) to investigate and compare transcriptional changes in the stems of tobacco upon inoculation with P. nicotianae strain race 0. We used two tobacco varieties: RBST (named from resistance to black shank and tobacco mosaic virus), which was resistant to the P. nicotianae strain race 0, and Honghuadajinyuan (HD), which was susceptible to P. nicotianae race 0. Samples were collected 12 and 72-hour post inoculation (hpi). Analysis of differentially expressed genes (DEGs) and significantly enriched GO terms indicated that several basic defense mechanisms were suppressed in both varieties, which included response to wounding (GO: 0009611), and defense response to fungus (GO: 0050832). We also found some genes that may especially be related to mechanisms of resistance in RBST, such as the one encoding a chitinase. These results will provide a valuable resource for understanding the interactions between P. nicotianae and tobacco plants.