So perhaps a starting point is to first look at the opening clause of the Mishna.
"Rabbi Jacob says: if one is studying while walking on the road and interrupts his study"
The first issue that is being criticised is the fact that a person is learning in a non-ideal scenario. Whilst on face value nowadays walking along the road doesn't seem so bad, Tosafos Yom Tov points to the fact that (at least at those times),the roads were places where danger lurked. So to be learning Torah in such a scenario is highlighted as a particular error. The idea being that one who forfeits the protective power of Torah, one leaves oneself vulnerable to potential danger. He additionally adds that while there are those who would say it is not dangerous, the fact that he is out and about in nature means he is a lot more likely to be distracted by the scenery.
So with that as a starting point - why then is such a person called out for 'mortal guilt'?
Rashi concurs with Tosafos Yom Tov that being out on the road is a dangerous exercise and as such, having relinquished the protection afforded to one who is engaged in Torah study he bears responsibility for whatever adversity he suffers on this danger-laden road. Rabbeinu Yonah similarly adds that by interrupting his learning by "שיחת חולין" - "mundane talk" he is thereby indicting himself.
The reasoning behind this strong condemnation of כְּאִלּוּ מִתְחַיֵּב בְּנַפְשׁוֹ is underlined by the Meiri who writes that since man by his nature is drawn to the mundane and meaningless, one seemingly minor interruption can lead to a series of distractions ultimately leading to the complete rejection of the yoke of Torah:
והטעם שטבעו של אדם נמשך אחר ההבלים והשיחות בטילות, וימשך ממנו בזה עד שיפרוק עול תורה לגמרי
Finally, it is written in Magen Avos how the Gemorah likens men to fish (refer to Chavakuk 1:14), and just as fish die when they come on to dry land, so too men die in a spiritual sense when they withdraw from Torah (he draws this from the gemorah in Avodah Zara 3b). As such one who who cuts his link to Torah (albeit fleetingly in this case) has severed his spiritual life support.